Effect of Intraduodenal Administration of Ursodeoxycholic Acid on Interdigestive Interaction between Gallbladder Motility, Pancreatic Secretion and Endocrine Activity

Abstract

Background: Gastroduodenal motorfunction, gallbladder motility, and pancreatic secretion are closely related during the interdigestive state. The extent to which application of ursodeoxycholic acid (UDC) influences this process is only partly understood. Aim: As UDC is widely used for the therapy of gallbladder stones and of cholestatic liver disease, we wanted to define the immediate effect of UDC on interdigestive gallbladder and antroduodenal motility, biliary-pancreatic secretion and hormone release in man. Methods: Interdigestive gastrointestinal function in 10 healthy males (26–35 years) was studied twice after 12-hour fasting on 2 different days. Antroduodenal motility was continuously recorded manometrically over a complete interdigestive migrating motor complex (MMC) cycle. Gallbladder volume was evaluated sonographically in 5- to 7-min intervals during the MMC cycle. Pancreatic and biliary secretion was determined by a standard duodenal perfusion technique measuring chymotrypsin, amylase, lipase and bile salts in duodenal aspirates every 15 min. Plasma levels of pancreatic polypeptide (PP) and motilin were determined by radioimmunoassay in 15-min intervals. On 2 separate days, 7–10 days apart, each subject received intraduodenally either 10 mg/kg UDC (pH 8) or placebo 30 min after the first recorded duodenal MMC cycle phase III. Results: With placebo, the fasting gallbladder volume decreased slightly from phase I (32 ± 8 ml) to the end of phase II (24 ± 13 ml), but increased significantly from 31 ± 14 ml (phase I) to 46 ± 11 ml (phase III) after intraduodenal UDC application (p < 0.01). Pancreatic secretion was significantly reduced after UDC application at the end of phase II (secretion of chymotrypsin 10 ± 3 U/min vs. 5 ± 2 U/min, p < 0.01). Serum levels of PP were also reduced by UDC during the entire MMC cycle. This reached statistical significance at the end of phase II (84 ± 8 pg/ml vs. 57 ± 14 pg/ml; p < 0.05) and during phase III (86 ± 19 pg/ml vs. 64 ± 22 pg/ml; p < 0.05), while motilin slightly increased during the MMC cycle after UDC application. UDC instillation did not affect antroduodenal motility. Conclusion: UDC exerts significant inhibitory effects on interdigestive gallbladder contractility, pancreatic secretion, and PP release. Whether these inhibitory effects are mediated by cholinergic pathways or other mechanisms requires further investigation.

Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction

“…Only diastolic blood pressure was slightly but significantly reduced ( Schiedermaier et al, 2000 ). As known from other studies, UDCA leads to an immediate ( Sailer et al, 1996 ; Schiedermaier et al, 2000 ; Neubrand et al, 2004 ) increase in gallbladder volume. The mechanism of this effect on a smooth muscle organ is still unclear; one explanation could be the inhibition of cholinergic pathways ( Neubrand et al, 2004 ).…”

“…As known from other studies, UDCA leads to an immediate ( Sailer et al, 1996 ; Schiedermaier et al, 2000 ; Neubrand et al, 2004 ) increase in gallbladder volume. The mechanism of this effect on a smooth muscle organ is still unclear; one explanation could be the inhibition of cholinergic pathways ( Neubrand et al, 2004 ). To what extent this effect on the gallbladder influences intestinal metabolism of BA is unclear.…”

“…Dysregulation of the neurotransmitter NPY, which enhances α 1 -adrenergic vasoconstriction, is also noted in the cirrhotic rat (Moleda et al, 2011). Decreased transcription of vasoconstrictor receptors does not seem to play a role (Neef et al, 2003).…”